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Sleep. 2013 Mar 1;36(3):431-46. doi: 10.5665/sleep.2466.

Common genetic variants in ARNTL and NPAS2 and at chromosome 12p13 are associated with objectively measured sleep traits in the elderly.

Author information

1
California Pacific Medical Center Research Institute, San Francisco, CA 94107-1728, USA.

Abstract

STUDY OBJECTIVES:

To determine the association between common genetic variation in the clock gene pathway and objectively measured acti-graphic sleep and activity rhythm traits.

DESIGN:

Genetic association study in two population-based cohorts of elderly participants: the Study of Osteoporotic Fractures (SOF) and the Osteoporotic Fractures in Men (MrOS) study.

SETTING:

Population-based.

PARTICIPANTS:

SOF participants (n = 1,407, 100% female, mean age 84 years) and MrOS participants (n = 2,527, 100% male, mean age 77 years) with actigraphy and genotype data.

INTERVENTIONS:

N/A.

MEASUREMENTS AND RESULTS:

Common genetic variation in 30 candidate genes was captured using 529 single nucleotide polymorphisms (SNPs). Sleep and activity rhythm traits were objectively measured using wrist actigraphy. In a region of high linkage disequilibrium on chromosome 12p13 containing the candidate gene GNB3, the rs1047776 A allele and the rs2238114 C allele were significantly associated with higher wake after sleep onset (meta-analysis: rs1047776 PADD = 2 × 10(-5), rs2238114 PADD = 5 × 10(-5)) and lower LRRC23 gene expression (rs1047776: ρ = -0.22, P = 0.02; rs2238114: ρ = -0.50, P = 5 × 10(-8)). In MrOS participants, SNPs in ARNTL and NPAS2, genes coding for binding partners, were associated with later sleep and wake onset time (sleep onset time: ARNTL rs3816358 P2DF = 1 × 10(-4), NPAS2 rs3768984 P2DF = 5 × 10(-5); wake onset time: rs3816358 P2DF = 3 × 10(-3), rs3768984 P2DF = 2 × 10(-4)) and the SNP interaction was significant (sleep onset time PINT = 0.003, wake onset time PINT = 0.001). A SNP association in the CLOCK gene replicated in the MrOS cohort, and rs3768984 was associated with sleep duration in a previously reported study. Cluster analysis identified four clusters of genetic associations.

CONCLUSIONS:

These findings support a role for common genetic variation in clock genes in the regulation of inter-related sleep traits in the elderly.

CITATION:

Evans DS; Parimi N; Nievergelt CM; Blackwell T; Redline S; Ancoli-Israel S; Orwoll ES; Cummings SR; Stone KL; Tranah GJ. Common genetic variants in ARNTL and NPAS2 and at chromosome 12p13 are associated with objectively measured sleep traits in the elderly. SLEEP 2013;36(3):431-446.

KEYWORDS:

Genetic; SNP; actigraphy; aging; circadian

Comment in

PMID:
23449886
PMCID:
PMC3571755
DOI:
10.5665/sleep.2466
[Indexed for MEDLINE]
Free PMC Article

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